Over 1.2 million Americans suffer a mild traumatic brain injury (mTBI) each year. The persistent physical, emotional and cognitive symptoms after mTBI significantly affect the quality of life of patients and their family members, with tremendous healthcare cost. However, the field still lacks diagnostic and prognostic tools for mTBI due to patients' negative findings in clinical imaging. Despite the progress in the investigation of neuronal and axonal injury, the neurovascular substrates of mTBI are still poorly understood. Evidence from molecular imaging suggests that mTBI causes regional disturbances in cerebral blood flow (CBF) and metabolism that account for the patients' neurocognitive and clinical symptoms. To date, the field lacks non- invasive means to assess regional brain tissue metabolism throughout the brain. Brain injury leads to uncoupling between brain metabolic demand and actual blood supply, so assessing CBF alone does not provide insight into brain tissue metabolism. To paint a more complete picture, one needs to measure both arterial blood supply and the oxygen saturation of draining veins to determine cerebral metabolic rate of oxygen (CMRO2), a key measure of brain tissue viability. For arterial blood supply measurement, we have developed methods for perfusion weighted imaging (PWI) analysis to accurately quantify absolute CBF. For venous blood oxygen saturation, we have developed a novel technique, known as susceptibility weighted imaging and mapping (SWIM), to measure the susceptibility of veins. Combining susceptibility with hematocrit, we can calculate the venous blood oxygenation. Our objective is to identify the neurovascular substrates in mTBI that account for patients' functional and neurocognitive symptoms. We will first calibrate the SWIM quantification of blood oxygenation in an arm vein by a point-of-care blood-gas oximeter and correct its partial volume problem in small veins of the brain (specific aim 1). Then, we will translate the brain imaging technique into mTBI patients to determine the regional CMRO2 (specific aim 2). Finally, we will determine the prognostic value of regional CMRO2 for mTBI patients' 6-month outcome (specific aim 3). Using both SWIM and PWI, we propose to assess brain tissue metabolism and its prognostic value in a cohort of 30 mTBI patients, from acute to chronic stages, in comparison with 30 demographically-matched controls. We hypothesize that CMRO2 will be abnormal in mTBI patients and that the magnitude of the abnormality will account for mTBI patients' neuropsychological and functional deficits. This will be the first time use of SWIM to measure oxygen saturation in mTBI patients. The deliverable of this project will be a set of non-invasive techniques for assessing regional brain tissue metabolism after mTBI, which will help physicians identify the brain tissue at risk for secondary complications as a potential treatment target to prevent long term deficits.